Synthesis, characterization and cytotoxic activity of gallium(III) complexes anchored by tridentate pyrazole-based ligands

J Inorg Biochem. 2010 May;104(5):523-32. doi: 10.1016/j.jinorgbio.2010.01.003. Epub 2010 Jan 20.

Abstract

Reactions of GaCl(3) with pyrazole-containing ligands of the pyrazole-imine-phenol (HL(1)-HL(3)) or pyrazole-amine-phenol (HL(4)-HL(6)) types led to the synthesis of well-defined [GaL(2)](+) homoleptic complexes (1-6). Complexes 1-6 were characterized by elemental analysis, ESI-MS (electrospray ionization-mass spectrometry), IR and NMR spectroscopies, and in the case of Complex 1 also by X-ray diffraction analysis. In complexes 1-3, the pyrazole-imine-phenolate ligands act as monoanionic chelators that coordinate to the metal in a meridional fashion, while 4-6 contain monoanionic and facially coordinated pyrazole-amine-phenolate ligands. Complexes 1-3 have a greater stability in solution compared to 4-6, which have shown a more pronounced tendency to release the respective ancillary ligands. The cytotoxicity of 1-6 and of the respective ligands (HL(1)-HL(6)) was evaluated against human prostate cancer cells PC-3 and human breast cancer cells MCF-7. The substituents of the phenolate rings strongly influenced the cytotoxicity of the compounds. Complexes 3 and 6 that contain chloride substituents at the phenolate rings have shown the highest cytotoxicity, including in the cisplatin-resistant PC-3 cell line. The cytotoxic profile of 3 and 6 is very similar to the one displayed by the respective anchor ligands, respectively HL(1) and HL(6). The cytotoxic activity of 3 and 6 is slightly increased by the presence of transferrin, and both complexes provoke cell death mainly by induction of apoptotic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms
  • Cell Line, Tumor / drug effects*
  • Chelating Agents / chemistry
  • Drug Screening Assays, Antitumor
  • Female
  • Gallium* / chemistry
  • Gallium* / pharmacology
  • Humans
  • Ligands*
  • Male
  • Molecular Sequence Data
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Prostatic Neoplasms
  • Pyrazoles* / chemical synthesis
  • Pyrazoles* / chemistry
  • Pyrazoles* / pharmacology
  • Transferrin / metabolism
  • X-Ray Diffraction

Substances

  • Chelating Agents
  • Ligands
  • Pyrazoles
  • Transferrin
  • pyrazole
  • Gallium